Younger and older adults often differ in underlying conditions, medications, and tolerability. A new EASD poster breaks down SURPASS-CVOT by age, focusing on cardiovascular events, not just how much weight was lost.
This is an age analysis within a large trial
The original trial compared tirzepatide with dulaglutide in participants who had type 2 diabetes and existing cardiovascular disease, with a median treatment duration of about 4 years. Its comparator was another active drug, not placebo.
The prespecified analysis presented on September 29 was divided into three groups: under 65 years, 65 years to less than 75 years, and 75 years and older. "Prespecified" means this age comparison was planned in advance, but it is still a subgroup analysis of the original trial.
Three age groups: how should the main cardiovascular results be viewed?
Cardiovascular death, myocardial infarction, and stroke combined make up the three-component endpoint in the poster. The hazard ratios for tirzepatide versus dulaglutide across the three age groups were 0.87, 0.98, and 0.87, in order.[1]
A hazard ratio of 1 can be understood as the two groups being comparable, and below 1 means the estimate points toward fewer events. But the 95% confidence intervals for all three age groups include 1, so one cannot simply pick out 0.87 and say "older adults have been proven to benefit by 13%."
Confidence intervals are like leaving a range around an estimate
In the group aged 75 years and older, the hazard ratio was 0.87, with an interval from 0.69 to 1.10. Based on these data, the true difference could be fewer events, or it could be no clear difference, or even slightly more. Looking only at 0.87 is not enough to settle the question.[1]
The interaction test between age and treatment did not show a clear difference. That means there is currently not enough evidence to say that the drug comparison result changes significantly across these three age groups. It does not mean that every age or every person has exactly the same result.
Add one more endpoint, and the answer may differ
The poster also looked at a four-component endpoint, adding coronary revascularization to the first three. In the group aged 75 years and older, the hazard ratio was 0.77, with an interval from 0.62 to 0.95.
This result does not contradict the three-component endpoint, because the events counted are different statistically. Once coronary revascularization is added, its numbers can no longer be called results for cardiovascular death, myocardial infarction, and stroke alone.
For older adults, whether treatment can be continued also matters
Among people aged 75 years and older, the poster reported discontinuation due to adverse events of about 21% and 17%, corresponding to tirzepatide and dulaglutide, respectively. When evaluating older patients, weight, blood glucose, gastrointestinal discomfort, and discontinuation should all be considered together.
This analysis adds evidence in older adults with diabetes at high cardiovascular risk. It did not study all healthy older adults, and treatment plans for every individual cannot be derived from it.
If there is no clear interaction difference across the three age groups, does that prove age is completely unimportant?
No. Failure to detect a difference may also be related to the number of people or the number of events. Age can still affect underlying conditions, kidney function, nutrition, and tolerability; this analysis only answers the treatment comparison in the corresponding trial.
When looking at subgroups, it is best to keep both the comparison value and the interval. When an interval crosses 1, a point estimate that looks favorable still carries uncertainty; one should also not pick only a secondary endpoint that reached significance to replace the primary endpoint.
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The tirzepatide catalog page provides information on related research materials. The clinical drug and follow-up conditions in the poster are different matters from catalog raw material supply.
Tirzepatide · Tirzepatide
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